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Congenital osteogenesis imperfecta-microcephaly-cataracts syndrome

MedGen UID:
337988
•Concept ID:
C1850184
•
Disease or Syndrome
Synonym: Osteogenesis imperfecta congenita microcephaly and cataracts
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0009803
OMIM®: 259410
Orphanet: ORPHA2772

Definition

A rare multiple congenital malformations/dysmorphic syndrome characterized by osteogenesis imperfecta with multiple prenatal bone fractures, joint laxity, severe microcephaly, and bilateral cataracts. Additional reported manifestations include dysmorphic facial features (such as blue sclerae, hypertelorism, and low-set ears), lissencephaly, hydrocephalus, and cardiac and genital anomalies. The syndrome is lethal <i>in utero</i> or shortly after birth. There have been no further descriptions in the literature since 1978. [from ORDO]

Clinical features

From HPO
Disproportionate short-limb short stature
MedGen UID:
342370
•Concept ID:
C1849937
•
Finding
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
See: Feature record | Search on this feature
Platybasia
MedGen UID:
45959
•Concept ID:
C0032209
•
Congenital Abnormality
A developmental malformation of the occipital bone and upper end of the cervical spine, in which the latter appears to have pushed the floor of the occipital bone upward such that there is an abnormal flattening of the skull base.
See: Feature record | Search on this feature
Pectus carinatum
MedGen UID:
57643
•Concept ID:
C0158731
•
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
See: Feature record | Search on this feature
Decreased calvarial ossification
MedGen UID:
322270
•Concept ID:
C1833762
•
Finding
Abnormal reduction in ossification of the calvaria (roof of the skull consisting of the frontal bone, parietal bones, temporal bones, and occipital bone).
See: Feature record | Search on this feature
Bowing of limbs due to multiple fractures
MedGen UID:
376722
•Concept ID:
C1850178
•
Finding
Curvature of the shafts of the long bones due to multiple fractures.
See: Feature record | Search on this feature
Multiple prenatal fractures
MedGen UID:
377844
•Concept ID:
C1853171
•
Finding
The presence of bone fractures in the prenatal period that are diagnosed at birth or before.
See: Feature record | Search on this feature
Pectus excavatum
MedGen UID:
781174
•Concept ID:
C2051831
•
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
See: Feature record | Search on this feature
Wormian bones
MedGen UID:
766814
•Concept ID:
C3553900
•
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
See: Feature record | Search on this feature
Microcephaly
MedGen UID:
1644158
•Concept ID:
C4551563
•
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
See: Feature record | Search on this feature
Thin skin
MedGen UID:
140848
•Concept ID:
C0423757
•
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
See: Feature record | Search on this feature
Developmental cataract
MedGen UID:
3202
•Concept ID:
C0009691
•
Congenital Abnormality
A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.
See: Feature record | Search on this feature
Blue sclerae
MedGen UID:
154236
•Concept ID:
C0542514
•
Finding
An abnormal bluish coloration of the sclera.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital osteogenesis imperfecta-microcephaly-cataracts syndrome
Follow this link to review classifications for Congenital osteogenesis imperfecta-microcephaly-cataracts syndrome in Orphanet.

Professional guidelines

PubMed

The etiology, clinical features, and treatment options of hemifacial microsomia.
Luo S, Sun H, Bian Q, Liu Z, Wang X
Oral Dis 2023 Sep;29(6):2449-2462. Epub 2023 Mar 13 doi: 10.1111/odi.14508. PMID: 36648381
Aetiology, diagnosis, and treatment of brachymetatarsia: a narrative review.
Fusini F, Alessandro M, Rava A, Kristijan Z, Felli L, Colò G
Musculoskelet Surg 2022 Jun;106(2):99-109. Epub 2021 Jul 15 doi: 10.1007/s12306-021-00720-z. PMID: 34268706
The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis.
Weiss K, Lazar HP, Kurolap A, Martinez AF, Paperna T, Cohen L, Smeland MF, Whalen S, Heide S, Keren B, Terhal P, Irving M, Takaku M, Roberts JD, Petrovich RM, Schrier Vergano SA, Kenney A, Hove H, DeChene E, Quinonez SC, Colin E, Ziegler A, Rumple M, Jain M, Monteil D, Roeder ER, Nugent K, van Haeringen A, Gambello M, Santani A, Medne L, Krock B, Skraban CM, Zackai EH, Dubbs HA, Smol T, Ghoumid J, Parker MJ, Wright M, Turnpenny P, Clayton-Smith J, Metcalfe K, Kurumizaka H, Gelb BD, Baris Feldman H, Campeau PM, Muenke M, Wade PA, Lachlan K
Genet Med 2020 Feb;22(2):389-397. Epub 2019 Aug 7 doi: 10.1038/s41436-019-0612-0. PMID: 31388190Free PMC Article

Recent clinical studies

Etiology

Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.
Priestley JRC, Deshwar AR, Murthy H, D'Agostino MD, Dupuis L, Gangaram B, Gray C, Jobling R, Pannia E, Platzer K, Prescott K, Redman M, Rippert AL, Rosenfeld JA, Scott DA, Wang YW, Schmederer Z, Dalal A, Sarma AS, Skraban C, Dowling JJ, Mendoza-Londono R, Slavotinek A, Bhoj EJ
Genet Med 2023 Aug;25(8):100863. Epub 2023 Apr 28 doi: 10.1016/j.gim.2023.100863. PMID: 37125634
Bruck Syndrome: Beyond the Obvious.
Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Glossoptosis.
Schweiger C, Manica D, Kuhl G
Semin Pediatr Surg 2016 Jun;25(3):123-7. Epub 2016 Feb 18 doi: 10.1053/j.sempedsurg.2016.02.002. PMID: 27301596
Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.
Barron MJ, McDonnell ST, Mackie I, Dixon MJ
Orphanet J Rare Dis 2008 Nov 20;3:31. doi: 10.1186/1750-1172-3-31. PMID: 19021896Free PMC Article
Collagenopathic cardiopathies.
Carcassi U, Passiu G
Ann Ital Med Int 1991 Oct-Dec;6(4 Pt 2):483-90. PMID: 1840815

Diagnosis

The etiology, clinical features, and treatment options of hemifacial microsomia.
Luo S, Sun H, Bian Q, Liu Z, Wang X
Oral Dis 2023 Sep;29(6):2449-2462. Epub 2023 Mar 13 doi: 10.1111/odi.14508. PMID: 36648381
Craniofacial Microsomia.
Birgfeld C, Heike C
Clin Plast Surg 2019 Apr;46(2):207-221. doi: 10.1016/j.cps.2018.12.001. PMID: 30851752
Glossoptosis.
Schweiger C, Manica D, Kuhl G
Semin Pediatr Surg 2016 Jun;25(3):123-7. Epub 2016 Feb 18 doi: 10.1053/j.sempedsurg.2016.02.002. PMID: 27301596
Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.
Barron MJ, McDonnell ST, Mackie I, Dixon MJ
Orphanet J Rare Dis 2008 Nov 20;3:31. doi: 10.1186/1750-1172-3-31. PMID: 19021896Free PMC Article
Osteogenesis imperfecta in the neonate.
Hackley L, Merritt L
Adv Neonatal Care 2008 Feb;8(1):21-30; quiz 31-2. doi: 10.1097/01.ANC.0000311013.71510.41. PMID: 18300735

Therapy

Evaluation of growth, puberty, osteoporosis, and the response to long-term bisphosphonate therapy in four patients with osteoporosis-pseudoglioma syndrome.
Karakilic-Ozturan E, Altunoglu U, Ozturk AP, Kardelen Al AD, Yavas Abali Z, Avci S, Wollnik B, Poyrazoglu S, Bas F, Uyguner ZO, Kayserili H, Darendeliler F
Am J Med Genet A 2022 Jul;188(7):2061-2070. Epub 2022 Apr 8 doi: 10.1002/ajmg.a.62742. PMID: 35393770
Novel Majeed Syndrome-Causing LPIN2 Mutations Link Bone Inflammation to Inflammatory M2 Macrophages and Accelerated Osteoclastogenesis.
Bhuyan F, de Jesus AA, Mitchell J, Leikina E, VanTries R, Herzog R, Onel KB, Oler A, Montealegre Sanchez GA, Johnson KA, Bichell L, Marrero B, De Castro LF, Huang Y, Calvo KR, Collins MT, Ganesan S, Chernomordik LV, Ferguson PJ, Goldbach-Mansky R
Arthritis Rheumatol 2021 Jun;73(6):1021-1032. Epub 2021 May 9 doi: 10.1002/art.41624. PMID: 33314777Free PMC Article
Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece.
Papadopoulos I, Bountouvi E, Attilakos A, Gole E, Dinopoulos A, Peppa M, Nikolaidou P, Papadopoulou A
Eur J Pediatr 2019 Mar;178(3):323-329. Epub 2018 Nov 29 doi: 10.1007/s00431-018-3299-3. PMID: 30499050
Craniofacial fibrous dysplasia: A 10-case series.
Couturier A, Aumaître O, Gilain L, Jean B, Mom T, André M
Eur Ann Otorhinolaryngol Head Neck Dis 2017 Sep;134(4):229-235. Epub 2017 Mar 14 doi: 10.1016/j.anorl.2017.02.004. PMID: 28302454
Anesthetic implications for the patient with osteogenesis imperfecta.
Oakley I, Reece LP
AANA J 2010 Feb;78(1):47-53. PMID: 20977129

Prognosis

BMP2 is a potential causative gene for isolated dextrocardia situs solitus.
Yogi A, Iemura R, Nakatani H, Takasawa K, Gau M, Yamauchi T, Yoshida M, Moriyama K, Ishii T, Hosokawa S, Yamada M, Suzuki H, Kosaki K, Kashimada K, Morio T
Eur J Med Genet 2023 Sep;66(9):104820. Epub 2023 Aug 11 doi: 10.1016/j.ejmg.2023.104820. PMID: 37572998
Bruck Syndrome: Beyond the Obvious.
Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Glossoptosis.
Schweiger C, Manica D, Kuhl G
Semin Pediatr Surg 2016 Jun;25(3):123-7. Epub 2016 Feb 18 doi: 10.1053/j.sempedsurg.2016.02.002. PMID: 27301596
New trends in cranio-orbital and midface distraction for craniofacial dysostosis.
Hopper RA
Curr Opin Otolaryngol Head Neck Surg 2012 Aug;20(4):298-303. doi: 10.1097/MOO.0b013e3283543a43. PMID: 22894998
Syndromes with congenital brittle bones.
Plotkin H
BMC Pediatr 2004 Aug 31;4:16. doi: 10.1186/1471-2431-4-16. PMID: 15339338Free PMC Article

Clinical prediction guides

BMP2 is a potential causative gene for isolated dextrocardia situs solitus.
Yogi A, Iemura R, Nakatani H, Takasawa K, Gau M, Yamauchi T, Yoshida M, Moriyama K, Ishii T, Hosokawa S, Yamada M, Suzuki H, Kosaki K, Kashimada K, Morio T
Eur J Med Genet 2023 Sep;66(9):104820. Epub 2023 Aug 11 doi: 10.1016/j.ejmg.2023.104820. PMID: 37572998
Bruck Syndrome: Beyond the Obvious.
Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis.
Weiss K, Lazar HP, Kurolap A, Martinez AF, Paperna T, Cohen L, Smeland MF, Whalen S, Heide S, Keren B, Terhal P, Irving M, Takaku M, Roberts JD, Petrovich RM, Schrier Vergano SA, Kenney A, Hove H, DeChene E, Quinonez SC, Colin E, Ziegler A, Rumple M, Jain M, Monteil D, Roeder ER, Nugent K, van Haeringen A, Gambello M, Santani A, Medne L, Krock B, Skraban CM, Zackai EH, Dubbs HA, Smol T, Ghoumid J, Parker MJ, Wright M, Turnpenny P, Clayton-Smith J, Metcalfe K, Kurumizaka H, Gelb BD, Baris Feldman H, Campeau PM, Muenke M, Wade PA, Lachlan K
Genet Med 2020 Feb;22(2):389-397. Epub 2019 Aug 7 doi: 10.1038/s41436-019-0612-0. PMID: 31388190Free PMC Article
Novel Mutations in PLOD2 Cause Rare Bruck Syndrome.
Lv F, Xu X, Song Y, Li L, Asan, Wang J, Yang H, Wang O, Jiang Y, Xia W, Xing X, Li M
Calcif Tissue Int 2018 Mar;102(3):296-309. Epub 2017 Nov 24 doi: 10.1007/s00223-017-0360-6. PMID: 29177700
Neonates with tongue-based airway obstruction: a systematic review.
Bookman LB, Melton KR, Pan BS, Bender PL, Chini BA, Greenberg JM, Saal HM, Taylor JA, Elluru RG
Otolaryngol Head Neck Surg 2012 Jan;146(1):8-18. Epub 2011 Sep 16 doi: 10.1177/0194599811421598. PMID: 21926259

Recent systematic reviews

Dental Manifestations of Ehlers-Danlos Syndromes: A Systematic Review.
Kapferer-Seebacher I, Schnabl D, Zschocke J, Pope FM
Acta Derm Venereol 2020 Mar 25;100(7):adv00092. doi: 10.2340/00015555-3428. PMID: 32147746Free PMC Article
An update on the role of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways in pediatric diseases.
Brunetti G, D'Amato G, Chiarito M, Tullo A, Colaianni G, Colucci S, Grano M, Faienza MF
World J Pediatr 2019 Feb;15(1):4-11. Epub 2018 Oct 20 doi: 10.1007/s12519-018-0198-7. PMID: 30343446
Complications of mandibular distraction osteogenesis for congenital deformities: a systematic review of the literature and proposal of a new classification for complications.
Verlinden CR, van de Vijfeijken SE, Jansma EP, Becking AG, Swennen GR
Int J Oral Maxillofac Surg 2015 Jan;44(1):37-43. Epub 2014 Aug 20 doi: 10.1016/j.ijom.2014.07.009. PMID: 25148931
The etiology of short stature affects the clinical outcome of lower limb lengthening using external fixation. A systematic review of 18 trials involving 547 patients.
Kim SJ, Pierce W, Sabharwal S
Acta Orthop 2014 Apr;85(2):181-6. doi: 10.3109/17453674.2014.899856. PMID: 24650027Free PMC Article
Neonates with tongue-based airway obstruction: a systematic review.
Bookman LB, Melton KR, Pan BS, Bender PL, Chini BA, Greenberg JM, Saal HM, Taylor JA, Elluru RG
Otolaryngol Head Neck Surg 2012 Jan;146(1):8-18. Epub 2011 Sep 16 doi: 10.1177/0194599811421598. PMID: 21926259

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